A Lysophospholipase D Pathway in the Metabolism of Ether-linked Lipids in Brain Microsomes

Microsomal preparations from rat brain in the presence of Mg2+ hydrolyzed the ethanolamine, choline, and phosphate moieties from 1-[1-14C]hexadecyl-sn-glycero-3-phosphorylethanolamine, 1-[1-14C]hexadec-1-enyl-sn-glycero-3-phosphorylethanolamine, and 1-[1-14C]hexadecyl-sn-glycero-3-phosphorylcholine. Studies of the hydrolysis of 1-[1-14C]-hexadecyl-sn-glycero-3-phosphorylethanolamine in this system indicated that the ethanolamine moiety was first removed by a phosphodiesterase to form 1-[1-14C]hexadecylglycero-3-phosphate which was then dephosphorylated to form 1-[1-14C]hexadecylglycerol. Only minimal hydrolysis occurred when the 2-positions of the substrates were acylated; otherwise the phosphodiesterase activity was similar to that of phospholipase D from plants. The occurrence of such a lysophospholipase D pathway has not been previously reported. When Ca2+ (5 mm) was added to the system instead of Mg2+ (5 mm), little, if any, stimulation occurred; higher concentrations of Ca2+ (25 mm) inhibited the reaction. Therefore, this reaction does not appear to be related to the Ca2+-stimulated base exchange reaction found in the brain by others.